The combination of quantitative faecal occult blood test and faecal calprotectin is a cost-effective strategy to avoid colonoscopies in symptomatic patients without relevant pathology.

BACKGROUND: Faecal occult blood test (FOBT) has demonstrated effectiveness in colorectal cancer (CRC) screening. Faecal calprotectin (FC) has proven efficient for evaluating activity in inflammatory bowel disease (IBD), but its value in CRC detection is less established. Most symptomatic patients have benign pathologies, but still undergo colonoscopy in many settings. AIMS: To evaluate the diagnostic accuracy and cost-effectiveness of the combination of FOBT plus FC in symptomatic patients. METHODS: Patients who completed colonic investigations and returned stool samples, on which FOBT and FC were performed, were recruited prospectively. CRC, advanced adenoma, IBD and angiodysplasia were considered as relevant pathologies. RESULTS: A total of 404 patients were included, of whom 87 (21.5%) had relevant pathologies. Sensitivity and specificity were 50.6% and 69.6% for FOBT, 78.2% and 54.4% for FC. Negative predictive value (NPV) was 90.1% for FC and 86.9% for FOBT. NPV for the combination of FOBT and FC was 94.1%, with a sensitivity and specificity of 88.5% and 50.3%. The area under ROC (receiver operator curve) (AUC) was 0.741 for FOBT, 0.736 for FC and 0.816 for the combination. The total cost for visits and procedures was €233,016 (€577/patient). Using a combination of FOBT and FC as pre-endoscopic tool allows colonoscopies to be reduced by 39.4%, reducing total costs by 20.5%. CONCLUSION: The combination of FOBT and FC has a better diagnostic accuracy compared with each test alone. Performing both tests before colonoscopy is a less costly and more effective strategy, reducing unnecessary procedures and complications.

Allergen components in diagnosing childhood hazelnut allergy: Systematic literature review and meta-analysis.

BACKGROUND: Hazelnut-specific IgE antibodies (sIgEs) in serum support the diagnosis of hazelnut allergy, but extract-based tests have low diagnostic specificity, commonly leading to over-diagnosis. Measuring sensitization to individual allergen components may enhance the diagnosis of hazelnut allergy. We systematically examined data on diagnostic accuracy of sIgE to commercially available hazelnut components to compare their individual contributions in diagnosing hazelnut allergy. METHODS: Seven databases were searched for diagnostic studies on patients suspected of having hazelnut allergy. Studies employing component-specific IgE testing on patients whose final diagnosis was determined by oral food challenges were included in the meta-analysis. Study quality was assessed as recommended by Cochrane. RESULTS: Seven cross-sectional studies and one case-control study were identified, seven presenting data on children (N = 635), and one on a mixed age population. Overall, the diagnostic accuracies of sIgE to both Cor a 9 and Cor a 14 were significantly higher than for Cor a 1-sIgE (P < .05). In children, the specificity of Cor a 14-sIgE at 0.35 kUA /L cutoff was 81.7% (95% CI 77.1, 85.6), and 67.3% (60.3, 73.6) for Cor a 9-sIgE. The specificities for Cor a 1-sIgE and hazelnut-sIgE were 22.5% (7.4, 51.2) and 10.8% (3.4, 29.8), respectively. The sensitivity of Cor a 1-sIgE (60.2% [46.9, 72.2]) was lower than for hazelnut extract-sIgE (95.7% [88.7, 98.5]), while their specificities did not differ significantly. CONCLUSION: sIgE to Cor a 14 and Cor a 9 hazelnut storage proteins increases diagnostic specificity in assessing hazelnut allergy in children. The combined use of hazelnut extract and hazelnut storage proteins may improve diagnostic value.

Accuracy of component-resolved diagnostics in peanut allergy: Systematic literature review and meta-analysis.

BACKGROUND: Peanut allergy diagnosis relies on clinical reactivity to peanut supported by detection of specific IgE (sIgE) antibodies. Extract-based sIgE tests have low specificity, so component-resolved diagnostics may complement whole-extract testing. METHODS: We systematically collected peanut allergen component data in seven databases and studied the diagnostic accuracy of peanut storage proteins (Arah1, 2, 3) and cross-reactive peanut proteins (Arah8 PR-10 and Arah9 lipid transfer protein) through meta-analyses. The systematic literature review included studies employing peanut components and oral food challenge (OFC) as reference standard in patients suspected of peanut allergy. Data for component sIgE at pre-defined detection thresholds were extracted and combined in random-effects bivariate meta-analyses. Risk of bias was assessed as recommended by Cochrane, with two additional quality items of importance for this review. RESULTS: Nineteen eligible studies presented data suitable for meta-analysis. In cross-sectional pediatric studies, the pooled sensitivity of Arah2-sIgE at 0.35 kUA /L cutoff was 83.3% [95% CI 75.6, 88.9] and specificity in diagnosing objective peanut allergy was 83.6% [95% CI 77.4, 88.4]. Compared with 0.1 and 1.0 kUA /L, this threshold provided the best diagnostic accuracy. At 0.35 kUA /L, Arah1 and Arah3 had comparable specificity (86.0% and 88.0%, respectively) but significantly lower sensitivity compared with Arah2 (37.0% and 39.1%, respectively; P < .05). CONCLUSION: sIgE to Arah2 can enhance the certainty of diagnosis and reduce the number of OFC necessary to rule out clinical peanut allergy in unclear cases.

Structured intervention plan including component-resolved diagnostics helps reducing the burden of food allergy among school-aged children.

BACKGROUND: Food allergies can substantially burden patients and families by negatively affecting finances, social relationships, and personal perceptions of health. This study was performed under the Finnish Allergy Programme aimed at reducing avoidance diets to foods in schoolchildren by 50%. The main goal of this study was to investigate how many children could be freed from diet restrictions in a Finnish school district through a diagnostic algorithm including component-resolved diagnostics and food challenge. The secondary aim was to provide a crude estimate of the burden of the elimination food diets in the region, and the savings associated with the proposed intervention. METHODS: A total of 205 children on a food avoidance diet according to the school register because of food allergy were invited into the study. One hundred and fifty-seven children were interviewed, tested for IgE to extracts and allergen components and food challenged in respective order. RESULTS: After two years, 12 children still had an avoidance diet and three of them were treated successfully with sOTI; the rest suspended their avoidance diet (n = 134) or dropped out of the study (n = 11). The cost of the elimination diets was estimated in 172 700€ per year at start and 13 200€ per year at the end of the study; total savings were 128 400€ yearly. CONCLUSIONS: The results demonstrate a 65% reduction of avoidance diets to foods in school-aged children, exceeding the 50% aim of the Finnish Allergy Programme. Therefore, it is possible to actively reduce the number of food allergy diagnoses that remain unmonitored in the society through a tailored diagnostic work-up.

Screening, diagnosis, and management of obstructive sleep apnea in dangerous-goods truck drivers: to be aware or not?

OBJECTIVE: The aims of this study were: to evaluate a homogeneous sample of truck drivers of dangerous goods (TDDGs) in order to assess the prevalence of obstructive sleep apnea (OSA), and to verify the secondary risk of motor vehicle accidents (MVAs) and near miss accidents (NMAs) in this population. METHODS: A sample of 283 male TDDGs was evaluated. None of the subjects reported OSA symptoms before screening. Clinical and physical evaluation, Epworth Sleepiness Scale (ESS), and the items on OSA from the Sleep Disorder Score (SDS) questionnaire were used to select subjects with suspicion of OSA. Polysomnography (PSG) was performed to confirm the diagnosis of OSA. The frequency of MVAs and NMAs was assessed at baseline for the whole sample, and also for the drivers with severe OSA after two years of continuous positive airway pressure (CPAP) treatment. RESULTS: The mean age of the sample was 42.3 ± 8.3 years. A total of 139 (49.1%) subjects had suspected OSA, and the PSG study confirmed the diagnosis in 35.7%. A significant association between OSA severity and NMAs was observed, and subjects with severe OSA showed a near five-fold increased risk of NMAs (OR = 4.745, 95% CI 1.292-17.424, p = 0.019). After two years of CPAP treatment, the rate of NMAs was comparable with drivers without OSA, showing the efficacy of therapy. CONCLUSION: This study showed an unexpected high prevalence of OSA in TDDGs. Untreated subjects with severe OSA had a significantly increased risk of NMAs. In professional drivers, screening, treatment, and management of OSA are mandatory for reducing road accident risk and improving road safety.

Meta-analysis of the prevalence of Leber hereditary optic neuropathy mtDNA mutations in Europe.

PURPOSE: A meta-analysis was conducted to estimate the prevalence of patients with molecularly confirmed Leber hereditary optic neuropathy (LHON) carrying any of the 3 primary mtDNA mutations (m.11778G>A, m.14484T>C, m.3460G>A) which cause this inherited form of blindness. METHODS: A literature search was conducted to identify primary reports with LHON prevalence data reported for Europe. The overall prevalence of LHON with molecularly confirmed diagnosis was evaluated by weighting the prevalence estimates of the individual studies by the inverse of their variance. RESULTS: Based on this meta-analysis of 5 European studies providing appropriate information, the estimated prevalence of LHON disease associated with the combined m.11778G>A, m.14484T>C, m.3460G>A mutations was ~1:45,000 (2.23 x 10(-5); 95% confidence interval [CI] 2.01-2.44 x 10(-5)). Patients with LHON carrying either the m.11778G>A or the m.3460G>A mutation have a more severe clinical presentation and a much lower chance of spontaneous recovery from vision loss compared to patients with the m.14484T>C mutation. The estimated prevalence for patients with LHON in Europe carrying either of these severe mutations (m.11778G>A or m.3460G>A) was ~1:65,000 (1.54 x 10(-5); 95% CI 1.33-1.74 x 10(-5)). CONCLUSIONS: Although this meta-analysis summarizes the existing prevalence data for the primary, disease-causing mitochondrial DNA mutations of LHON in Europe, there is still a clear lack of reliable primary epidemiologic data for this devastating ophthalmologic disease.

Unequal group variances in microarray data analyses.

MOTIVATION: In searching for differentially expressed (DE) genes in microarray data, we often observe a fraction of the genes to have unequal variability between groups. This is not an issue in large samples, where a valid test exists that uses individual variances separately. The problem arises in the small-sample setting, where the approximately valid Welch test lacks sensitivity, while the more sensitive moderated t-test assumes equal variance. METHODS: We introduce a moderated Welch test (MWT) that allows unequal variance between groups. It is based on (i) weighting of pooled and unpooled standard errors and (ii) improved estimation of the gene-level variance that exploits the information from across the genes. RESULTS: When a non-trivial proportion of genes has unequal variability, false discovery rate (FDR) estimates based on the standard t and moderated t-tests are often too optimistic, while the standard Welch test has low sensitivity. The MWT is shown to (i) perform better than the standard t, the standard Welch and the moderated t-tests when the variances are unequal between groups and (ii) perform similarly to the moderated t, and better than the standard t and Welch tests when the group variances are equal. These results mean that MWT is more reliable than other existing tests over wider range of data conditions. AVAILABILITY: R package to perform MWT is available at http://www.meb.ki.se/~yudpaw

Professional shift-work drivers who adopt prophylactic naps can reduce the risk of car accidents during night work.

STUDY OBJECTIVES: Night work can be dangerous because both circadian sleep propensity (process C) and sleep pressure due to the prolonged wakefulness (process S) contribute to the reduction of vigilance levels. As naps are a countermeasure to sleepiness, this study evaluates the role they play in preventing sleep-related accidents in Italian shift-working police drivers. DESIGN/SETTING/PARTICIPANTS: The study concerns highway car accidents that occurred to Italian shift-working police drivers; it was performed in 2 steps: a retrospective analysis of the overall number of accidents that occurred during the years 1993--1997 (n, 1195), followed by a validation analysis of a smaller cohort of accidents prospectively collected during 2003 (n, 84). INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: RETROSPECTIVE ANALYSIS: The influence of process S, process C, driver characteristics, and context conditions on accident risk, estimated by means of Cox hazard regression, revealed that nighttime accident risk was mainly influenced by process S levels. Consequently, an experimental mathematical model linking the hourly observed number of accidents to process S levels was designed. Its generalization to the theoretical case of drivers omitting naps showed an increase of about 38% of accidents. PROSPECTIVE ANALYSIS: In order to validate our results, we compared retrospective and prospective sleep patterns: no statistical difference was found. Again, the hourly number of accidents increased with homeostatic sleep pressure; the theoretical efficacy of napping was quantified in 48% accidents decrease. CONCLUSIONS: Our data seem to confirm that napping before working a night shift is an effective countermeasure to alertness and performance deterioration associated with night work. Moreover, this self-initiated behavior could have a prophylactic efficacy in reducing the number of car accidents.

Sleepiness and sleep disorders in shift workers: a study on a group of italian police officers.

STUDY OBJECTIVES: evaluation of shift-work effect on sleepiness, sleep disorders, and sleep-related accidents in a population of police officers. DESIGN: Aquestionnaire-based survey was used to gather information on age and physical characteristics, working conditions, sleep problems, and accidents. Sleepiness was measured by the Epworth Sleepiness Scale (ESS) while the presence of sleep disorders was evaluated by a score (SDS) drawn from indicators of insomnia, breathing disorders, periodic limb movements and restless legs syndrome, and hypersomnia. The effects of age, gender, body mass index, working conditions, and seniority on ESS, SD score, and accidents were analyzed by linear and logistic regression. SETTING: The self-administered questionnaires were filled in by police officers in the district of Genoa (Italy). PARTICIPANTS: 1,280 police officers: 611 shift workers (SW) and 669 non-shift workers (NSW). INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: The ESS score was not higher in SW than in NSW, while the SDS was significantly influenced by shift-work conditions and seniority in shift work. The occurrence of sleep-ascribed accidents was significantly increased in the SW group and related to the presence of indicators of sleep disorders. There was evidence for sleep disorders in 35.7% of SW and in 26.3% of NSW. CONCLUSIONS: Shift-work conditions and seniority may enhance sleep disorders and may favor sleep-related accidents, but they do not influence ESS score. Stressful conditions could cause sleepiness to be underestimated, or else they might overcome sleepiness. However, our data should alert occupational health physicians for the diagnosis and prevention of possible undetected intrinsic sleep disorders, which could possibly worsen shift workers' health and increase the risk of accidents.